The cytoskeleton in 'couch potato-ism': Insights from a murine model of impaired actin dynamics.

The cytoskeleton in 'couch potato-ism': Insights from a murine model of impaired actin dynamics. Exp Neurol. 2018 Apr 20;: Authors: Gertz K, Uhlemann R, Foryst-Ludwig A, Barrientos RM, Kappert K, Thöne-Reineke C, Djoufack P, Kirschbaum C, Fink KB, Heinz A, Kintscher U, Endres M, Kronenberg G Abstract Evidence for a critical pathophysiological role of aberrant cytoskeletal dynamics is being uncovered in a growing number of neuropsychiatric syndromes. A sedentary lifestyle as well as overt psychopathology is prevalent in patients with the metabolic syndrome. Using mice deficient in gelsolin (Gsn-/-), a crucial actin-severing protein, we here investigated reduced actin turnover as a potential common driver of metabolic disturbances, sedentary behavior, and an anxious/depressive phenotype. Gelsolin deficiency resulted in reduced lifespan. As compared to wildtype controls, Gsn-/- mice (~ 9 weeks) fed a high-fat diet (HFD) over a span of 12 weeks showed increased body weight gain, fat mass, hepatic steatosis, and adipocyte hypertrophy as well as a significantly reduced respiratory quotient. Moreover, increased rigidity of the actin cytoskeleton in mice on HFD induced mRNA expression of Acc1, Acc2, Fasn, and Lipe, key genes involved in fatty acid metabolism in the liver. Glucose tolerance and insulin sensitivity were worsened in Gsn-/- HFD relative to Gsn+/+ HFD mice. Hypertension in Gsn-/- mice was associated with reduced endothelial NO s...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research